Direct targeting of β-catenin in the Wnt signaling pathway: Current progress and perspectives

Area of Science:

• Oncology
• Molecular Biology
• Drug Discovery

Background:

• Aberrant Wnt/β-catenin signaling is implicated in various cancers, promoting recurrence, metastasis, and immune evasion.
• Targeting β-catenin, the pathway's central component, offers a promising therapeutic strategy but faces significant challenges.

Purpose of the Study:

• To identify potential small-molecule binding sites in β-catenin.
• To summarize existing small molecules that directly target β-catenin.
• To review structure-based inhibitor development, structure-activity relationships, and biological activities.

Main Methods:

• Characterization of β-catenin binding sites.
• Literature review of small molecules targeting β-catenin.
• Analysis of structure-activity relationships and biological data for inhibitors.

Main Results:

• Identification of potential druggable pockets within β-catenin.
• Compilation of a compendium of bioactive small molecules directly interacting with β-catenin.
• Overview of inhibitor optimization strategies and their efficacy.

Conclusions:

• Direct targeting of β-catenin is a viable, albeit challenging, approach for cancer therapy.
• Understanding β-catenin's structure and inhibitor interactions is crucial for future drug development.
• This review provides a foundation for advancing β-catenin-targeted cancer drug discovery.